A cohort of 240 Bedouin infants will be followed from birth to age two years, to examine the environmental, agent and host characteristics, and the interactions between them, leading to the range of clinical manifestation observed in Giardia lamblia (GL), Cryptosporidium (CR), and E. coli infections. Using novel methods of detection which are more sensitive than the methods available to date we will be able to define the factors causing GL infection in infants and children to be non- pathogenic in endemic areas. The factors to be examined include age at first exposure, intensity and frequency of repeat exposures, the nutritional status of the infants, previous diarrheal disease, passive immunity acquired through breast feeding, the immunological status of the infants, both humoral and cellular, and the characteristics of Giardia strains. The project will examine how GL carriage modulates and diminishes infections with other enteric pathogens, or their clinical manifestations. We will also determine why CR infections, on the other hand, often lead to persistent diarrhea. Possible explanations sought will include subnormal immunologic status, inadequate immunologic response associated with deficient nutritional status, high frequency of infections in general, or infections with multiple enteric agents, in particular. In the proposed program we will also have a unique opportunity to examine in a Middle-Eastern population, with diarrheal disease patterns of developing nations, the role of different categories of E. coli, thus contributing knowledge essential for the development of new vaccines. Another major contribution of this project is the demonstration, using a controlled intervention trial, that rates of enteric infections in infants and young children living in semi-urban settlements, in suboptimal environmental conditions, can be lowered by educational intervention methods aimed at reducing the direct exposure of the children and their food to enteric organisms. The intervention methods used will be transferable to other newly urbanized high risk populations.